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. 2022 Aug 15;128(16):3090-3098.
doi: 10.1002/cncr.34349. Epub 2022 Jun 9.

Risk-reducing surgery in unaffected individuals receiving cancer genetic testing in an integrated health care system

Sarah Knerr  1 , Boya Guo  1 , Kathleen F Mittendorf  2 , Heather Spencer Feigelson  3 , Marian J Gilmore  2 , Gail P Jarvik  4 , Tia L Kauffman  5 , Erin Keast  5 , Frances L Lynch  5 , Kristin R Muessig  2 , Sonia Okuyama  6 , David L Veenstra  7 , Jamilyn M Zepp  2 , Katrina A B Goddard  2 , Beth Devine  7
Affiliations

Risk-reducing surgery in unaffected individuals receiving cancer genetic testing in an integrated health care system

Sarah Knerr et al. Cancer. .

Abstract

Background: Germline genetic testing enables primary cancer prevention, including through prophylactic surgery. We examined risk-reducing surgeries in unaffected individuals tested for hereditary cancer susceptibly between 2010 and 2018 in the Kaiser Permanente Northwest health system.

Methods: We used an internal genetic testing database to create a cohort of individuals who received tests including one or more high-penetrance hereditary cancer susceptibility gene. We then identified, after testing, bilateral mastectomy, bilateral salpingo-oophorectomy (BSO), and total hysterectomy procedures in electronic health record and claims data through 2019. We describe surgery utilization by genetic test results and National Comprehensive Cancer Network (NCCN) guidelines.

Results: The cohort included 1020 individuals, 16% with pathogenic/likely pathogenic (P/LP) variants in one or more of the following genes: BRCA1, BRCA2, CHEK2, APC, MUTYH, ATM, MSH2, PALB2, BRIP1, MLH1, MSH6, EPCAM, FLCN, RAD51C, RAD51D, or TP53. Among individuals with P/LP variants making them candidates for mastectomy, BSO, or hysterectomy per NCCN guidelines, 34% (33/97), 24% (23/94), and 8% (1/12), respectively, underwent surgery during follow-up. Fifty-three percent (18/37) of hysterectomies were among APC, BRCA1, and BRCA2 P/LP variant heterozygotes, typically concurrent with BSO. Three individuals with variants of uncertain significance (only) and 22 with negative results had prophylactic surgery after genetic testing.

Conclusions: Uptake of risk-reducing surgery following usual care genetic testing appears to be lower than in studies that actively recruit high-risk patients and provide testing and follow-up care in specialized settings. Factors in addition to genetic test results and NCCN guidelines motivate prophylactic surgery use and deserve further study.

Keywords: genetic testing; hereditary cancer; primary prevention; prophylactic surgery; risk management.

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Conflict of interest statement

Conflict of interest: The authors made no disclosures.

Figures

Figure 1.
Figure 1.
Cohort construction.
See this image and copyright information in PMC

References

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